Background and rationale: Beta-lactam antibiotics are largely administered by bolus dosing, despite displaying time-dependent pharmacokinetics and pharmacodynamics and there being a strong rationale for continuous administration. The randomised controlled trials conducted to date comparing the mode of beta-lactam administration have been inconclusive and limited by non-equivalent dosing, unblinded administration and small sample sizes. Objective: A multicentre, randomised controlled trial (the Beta-lactam Infusion Group [BLING] II study) is currently under way, comparing continuous infusion to standard bolus administration of beta-lactam antibiotics in critically ill patients, independent of dose. Design, settings, participants and interventions: BLING II is a Phase IIB, double-blinded, randomised controlled trial recruiting 420 intensive care unit patients with severe sepsis to receive one of three beta-lactam study antibiotics (ticarcillin-clavulanate, piperacillin-tazobactam or meropenem) by either continuous infusion or intermittent bolus administration. Main outcome measures: The primary outcome is ICU-free days at Day 28. Secondary outcomes include 90-day survival, clinical cure 14 days after study antibiotic cessation, organ failure-free days at Day 14 and duration of bacteraemia. Results and conclusions: The study started in July 2012 and will provide clinical evidence as to whether continuous infusion of beta-lactam antibiotics is superior to intermittent bolus administration in critically ill patients with severe sepsis. A Phase III study powered for a survival end point may be justified, based on the results of our study.